Cell Therapy Modulates Expression of Tax1-Binding Protein 1 and Synaptotagmin IV in a Model of Optic Nerve Lesion

Abstract

Bone marrow mononuclear cells (BMMCs) have been used with considerable success to improve regeneration and/or functional recovery in animal models of neurologic diseases. Injected into the host, they migrate to the damaged areas and release cytokines and/or trophic factors, which are capable of altering the genetic program of the injured tissue cells. In this study, there was a search for genes with altered expression in a model of optic nerve crush and cell therapy. Optic nerve crush was followed by an intravitreous injection of BMMCs or vehicle in adult rats. After 14 days, we obtained a transcriptome screening of the retinas using differential display and automatic sequencing, followed by q-PCR, Western blot, and immunohistochemistry of selected genes and proteins. Among the differentially displayed genes, transcription of the antiapoptotic Tax1-binding protein 1 (Tax1BP1) and Synaptotagmin IV (Syt IV), an immediate early gene, is increased in the treated group. Tax1BP1 expression is robust in the ganglion cell layer and is significantly increased by cell therapy. Syt IV is expressed by activated Müller cells and astrocytes in the retina and optic nerve, without changes in protein levels among the groups. Tax1BP1 and Syt IV transcription and/or expression are differently modulated by optic nerve crush and BMMC treatment, and might be related to neuronal damage and cell-therapy effects in the retina. The increased expression of Tax1BP1 in the treated eyes could be involved in the neuroprotective effects of BMMCs that were described previously by our group.